Research on the controlled differentiation of ESC, for example to HSC, is advancing rapidly [21, –23]; therefore, a proactive debate on the practical and ethical pros and cons of the type 2 case is important. Can this procedure be morally justified and, if so, under which conditions?
The first advantage of PGD/HLA testing type 2 is that it will increase the number of therapeutic options. For those parents who cannot support another child, this procedure may be the only real option. Other parents, if given the choice, may prefer PGD/HLA testing type 2 to type 1, especially if they consider their family to be complete. For these parents, the type 1 case will be second best.
Second, PGD/HLA testing type 2 may have substantial medical/practical advantages if it were to have a higher success rate than the type 1 procedure in terms of saving the diseased sib. Clearly, this remains to be seen. One may need fewer embryos to obtain the cells needed for transplantation: the THBR after PGD/HLA is only 10% ([12, 13] and our unpublished data), whereas the derivation rate of a stable ESC line from an embryo after PGD is approximately 20% . Furthermore, a successful pregnancy takes 9 months, whereas the type 2 procedure may be less time consuming; generally, it takes 3 months to derive and characterize a stable ESC line and 2–3 weeks to differentiate these cells into a heterogeneous population containing hematopoietic progenitor cells [19, 24]. However, before it can be used for HSC transplantation in patients, a high number of cells would be required, and the safety of the ex vivo expansion and the transplantation still need to be evaluated. Finally, the availability of HLA-matched ESC could perhaps make it possible in the long-term to derive other tissues/organs in case another transplantation is required (e.g., kidney).
Third, the child-related objections and concerns regarding type 1 would be circumvented. These include the presumed instrumental use of children and the possible psychosocial and medical risks for the future donor. As a consequence, the debate about the conditions to be imposed in view of the additional complications inherent in the variants mentioned above would become irrelevant. The cases of a diseased parent, a nonhereditary disorder, and possible additional tissue donation would become nonissues in the context of PGD/HLA testing type 2. Likewise, the selected HLA type would never imply a health risk for future donors.
The primary normative issue regarding PGD/HLA testing type 2 concerns the creation of (human) preimplantation embryos solely for so-called instrumental use, particularly, to obtain ESC/HSC for cell therapy. It is important to distinguish between a legal and an ethical perspective. Many countries prohibit the creation of embryos for instrumental use in accordance with Article 18 of the European Convention on Human Rights and Biomedicine of the Council of Europe: (1) Where the law allows research on embryos in vitro, it shall ensure adequate protection of the embryo; (2) The creation of human embryos for research purposes is prohibited . At the same time, many countries accept the instrumental use of so-called surplus or spare embryos, which remain after IVF or IVF/PGD. From an ethical perspective, the question arises as to whether there is a decisive moral difference between the instrumental use of spare embryos and the creation of embryos for instrumental use . Why accept the former and categorically prohibit the latter? The ethical and societal debate about this issue often focuses exclusively on the moral status and the protection of the embryo. It is important, however, not to treat embryos as entities disconnected from their source, as if the female body is not involved. After all, embryos come from oocytes, and oocytes come from women. The ethical debate about creating embryos for instrumental use should, therefore, consider both the moral status of the embryo and the interests and welfare of women, especially candidate oocyte donors. According to Raymond, the feminist perspective, which focuses on women/oocyte donors involved, is as important as the fetalist perspective, which focuses on the embryo .
From a fetalist perspective, there are good reasons to consider that there is no fundamental difference between the instrumental use of spare embryos and the creation of embryos for instrumental use, since the moral status of these embryos is the same. However, there is a difference with respect to the intention at fertilization. This difference, however, is only gradual; it is a misunderstanding to assume that in the context of regular IVF, each embryo is created as a goal in itself. The loss of some spare IVF embryos is a calculated risk beforehand. It can, therefore, be argued that the creation of embryos for instrumental use, just as the use of spare embryos, can be morally justified on grounds of proportionality (i.e., the instrumental use of embryos should serve an important goal or, more specifically, an important health interest) and subsidiarity or necessity (i.e., there is no suitable embryo-saving alternative to reach this goal). Assuming that the moral status of the early embryo (which will be used at day 5) is relatively low, the use of embryos for life-saving cell therapy is clearly proportional. Regulations in some countries (e.g., the U.K. and Belgium) permit somatic cell nuclear transfer for therapeutic purposes, so-called therapeutic cloning. It would be inconsistent, then, not to allow the instrumental use of embryos for other types of cell therapy, like in PGD/HLA testing type 2.
Critics of PGD/HLA testing type 2 would possibly argue that this strategy is contrary to the principle of subsidiarity, pointing to various alternative options that are embryo-saving. The first option would be to invest further in cell banks in order to maximize the HLA types available for treatment. It seems impossible, however, to guarantee that cell banks would be able to provide matched cells for all patients, irrespective of their HLA type . Thus, PGD/HLA testing type 2 may still be needed as a last resort in individual cases. Another alternative, which limits the loss of embryos, is PGD/HLA testing type 1, as the matched and healthy embryos will be transferred. Can one indeed convincingly argue that PGD/HLA testing type 2 is morally unjustified if type 1 would be possible? This restrictive interpretation of the principle of subsidiarity is not reasonable in view of the possible advantages of type 2; this strategy may better meet the interest of both the diseased sib (as the procedure may have a better success rate) and the parents (they will have more options). Furthermore, type 2 avoids the psychological and medical risks of type 1 for the donor child. In other words, the restrictive interpretation of the principle of subsidiarity illustrates a one-dimensional approach that a priori gives priority to avoiding or minimizing loss of preimplantation embryos. A permissive interpretation of this principle, then, seems to be justified.
Obviously, it is important to acknowledge that the difference between PGD/HLA testing type 1 and type 2 is only gradual, as the loss of embryos can be 75%, 81.25%, or 87.5% in the first case (depending on whether the embryo is only tested for its HLA type, in combination with an autosomal recessive disorder, or an X-linked disorder by sexing, respectively) and 100% in the latter. The argument that the first is acceptable whereas the latter is not is difficult to accept.
From a feminist perspective, the production of embryos for instrumental use is controversial mainly because both the hormones given in order to induce a “super-ovulation” and the oocyte aspiration are burdensome and carry some risk for women (the oocyte donors). Critics consider this to be especially problematic when women are asked to donate oocytes for research purposes. They argue that the benefits of research are uncertain, if not speculative; the risks and burdens of the procedure for the donor are disproportional and, therefore, unjustified. However, this criticism seems to be less relevant for the ethics of oocyte donation for therapeutic purposes, as in PGD/HLA testing type 2. In this case, the risks and burdens of oocyte donation seem to be proportional in view of the benefit to be gained, that is, saving the woman's child. It would be inconsistent to accept PGD/HLA testing type 1 and, at the same time, to reject type 2 because of the risks/burdens of the latter to women involved. One may even argue that type 2 is less burdensome for women who would prefer not to have another pregnancy and child.